NANETS2025 18th Annual Multidisciplinary NET Medical Symposium NANETS 2025 Basic Science (10 abstracts)
A SST14 based T-cell engager for the treatment of neuroendocrine tumors
Eleonora Pelle 1 , Mauro Cives 2 , Jaydira Del Rivero 8 , Elliot Medina 3 , Nada Chaoul 2 , Suresh Kumar Gabriella d’Angelo 2 , Charlotte C. Mason 3 , Sebastian A. Snedal 4 , Xiomar E. Bustos-Perez 4 , Gabriele Maiorano 5 , Vincent C. Luca 3 , Patrick Hwu 6 , Daniel Abate-Daga 7 & Jonathan Strosberg 1
1Department of GI Oncology, Moffitt Cancer Center, Tampa, Florida, USA; 2Department of Interdisciplinary Medicine, University of Bari Aldo Moro, Bari, Italy; 3Department of Drug Discovery, Moffitt Cancer Center, Tampa, Florida, USA; 4Department of Immunology, Moffitt Cancer Center, Tampa, Florida, USA; 5Institute of Nanotechnology NANOTEC, National Research Council, Lecce, Italy; 6Moffitt Cancer Center, Tampa, Florida, USA; 7Departments of Immunology and Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida, USA; 8Developmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA
Background: Somatostatin receptor 2 (SSTR2) is overexpressed and currently used as a therapeutic target in well-differentiated neuroendocrine tumors (NETs). We designed a novel bispecific T-cell engager targeting SSTR2 via Somatostatin-14 (SST-14), linked with a scFV-based anti-CD3.
Methods: 293T cells expressing SSTR2-GFP or mock-GFP as control, the pancreatic NET cell line BON1, and patient-derived tumoroids from pancreatic NETs were used as target cells, while T cells enriched from PBMCs of healthy donors were used as effector cells. As an alternative, autologous tumor-infiltrating lymphocytes (TILs) and peripheral blood T cells from patients were used. Flow cytometry and ImageStream were used to assess the molecule’s interaction with CD3 and SSTR2, and immune synapse formation. T-cell activation and cytotoxicity induced by the engager were measured using ELISA and real-time live-cell imaging. The effect of the molecule alone on tumoroids was quantified by bioluminescence and octreotide was used as control. Cibacron blue–agarose beads coated with 100 µg of albumin were used to detect the interaction between the engager and albumin, and a scrambled SS14 engager was used as a control.
Results: The T-cell engager interacts with the CD3 on T-cells and the SSTR2 on target cells between 100nM and 20nM, inducing the formation of immunological synapses upon interaction. The molecule significantly increases IFN-γ, TNF-α, and Granzyme-B secretion when T cells are co-cultured with SSTR2+ 293T cells or BON1cell line. A similar effect is observed when patient-derived tumoroids are cocultured with autologous T cells or TILs. Moreover, at 20 and 100 nM, the engager shows dose-dependent cytotoxicity against SSTR2+ 293T cells in the presence of T cells, which is specific for the presence of the SSTR2. The molecule showed an intrinsic antiproliferative effect on patients derived tumoroids, which was comparable to octreotide. It also exhibited specific binding to albumin, in contrast to the control
Conclusions: This engager elicits a dose-dependent T cell response against several SSTR2-expressing cells, including NET cell lines and patient derived organoids. In the absence of T cells, the molecule retains its SST14-derived antiproliferative activity, which resembles that of octreotide.
Abstract ID #33480
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2026 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more